The main objective of this proposal is to provide the groundwork for establishing the chick embryo as an experimental model to study factors that regulate the development of monoaminergic neurons in the central nervous system. The chick embryo offers numerous advantages for such investigations because of its ease of accessibility as well as its isolation from maternal influences during pharmacological studies. Towards this objective, the specific aims of this proposal include an extensive analysis of the early development of central serotonergic (5-HT) neurons, a representative component of the monoaminergic neuronal system in the chick embryo. The ontogenesis of 5-HT systems will be examined from 3 perspectives. (1) The morphological development of 5-HT neurons will be described immunocytochemically (employing antibodies to 5-HT) to investigate the initial location of 5-HT neurons, their pattern of neuronal migration and their formation of projection pathways. (2) The time of neuronal genesis (time of origin) of identified 5-HT neurons will be determined by long survival 3H-thymidine autoradiography combined simultaneously with anti-5-HT immunocytochemistry. (3) In an attempt to resolve the ultimate fate of cells that transiently accumulate 5-HT in the early chick neural tube, the mitotic activity of these cells will be examined by short survival 3H-thymidine autoradiography in combination with anti-5HT immunocytochemistry in order to compare the time at which these cells cease division with the time of origin of 5-HT neurons. Overall, these research projects are designed to provide the background information required for future experiments in the chick embryo that will investigate processes that regulate the earliest aspects of monoaminergic neuronal ontogenesis. These studies will attempt to examine factors that influence the timing of neurotransmitter phenotype determination and expression, when these events occur in relation to the last mitotic division, and whether or not there is a plasticity in the phenotype selection that exists during further embryonic development. The results from the present proposal as well as from future studies will also provide the basis for establishing the chick embryo as a model for assessing the potential hazards of drugs such as antidepressants and tranquilizers prescribed for pregnant women.